1. Field of the Invention
This invention relates to chemical analogs of steviolmonoside which are formed from the sweet glycoside, stevioside; which are themselves sweet and useful as sweeteners; and which do not degrade under conditions of use to form physiologically undesirable steviol as do stevioside and steviolmonoside.
2. The Prior Art
The leaves of the Paraguayan shrub Stevia rebaudiana Bertoni have long been known to be sweet. A sweet crystalline glycoside has been isolated from these leaves. This compound, named stevioside by the Union International de Chimie in 1921, has been reported to be about 300 times as sweet as sucrose by Bridel et al., Compt. Rend., 192, 1123-5 (1931) and J. Pharm. Chim., 14(3), 99-113; 14 (4),154-161 (1931). Mosettig et al. reported the absolute configuration of stevioside as shown in general formula I. ##STR2## in J. Am. Chem. Soc., 85, 2305-2309 (1963). This material has attracted substantial interest as a potential sweetener, particularly in the orient where its plant source is now cultivated and where crude stevioside-containing extracts are used as sweeteners. (see Japanese Pat. Nos. 51-52200; 52-47956, 7 and 9; 52-51069; 52-57198 and 9 and 52-62300.)
Tanaka, et al., have shown in Chem Pharm Bull 25, 2466-7 (1977) that stevioside undergoes selective enzymatic conversion to steviol-13,19-bioside (II) in the presence of Takadiastase Y. This material can be converted to steviolmonoside (III) by treating with base. ##STR3##
Stevioside's acceptance in the United States has been slow. Possibly, this is because its sweet taste is contaminated by a substantial degree of bitterness. (Bridel et al., above). It also may be due to concerns about the compound's safety.
In 1966, P. V. Vignais and coworkers reported the results of a study concerned with elucidation of the mode of action of the respiratory toxin, atractyligenin. Included in their study were several compounds of related structure including steviol (IV), the aglycone of stevioside and steviolmonoside. ##STR4## Surprisingly, in cell mitochrondria, steviol was found to be an even more potent inhibitor of ATP synthetase than atractyligenin. (Biochim. Biophys. Acta, 118, 465-483 (1966).) In addition, steviol is reported to exhibit antiandrogenic effects (Dorfman, R. I., et al., Endocrinology, 67, 282-285 (1965)). Clearly, if stevioside was converted to steviol in vivo, significant toxicity may be expected. Recent results suggest the likelihood that stevioside or steviolmonoside would be largely converted to steviol in vivo, and further that the steviol thus produced would subsequently be completely absorbed through the gastrointestinal tract wall. (R. Wingard, J. Dale, J. Brown, R. Hale, Experientia, 36, 519, (1980)). Thus, as a result of a combination of the Vignais and Wingard work, it may be concluded that, with widespread use, stevioside may be expected to exhibit significant acute toxicity. If, however, stevioside's metabolism to steviol could be prevented, that is if a potently sweet analog could be developed which was not degraded to steviol, safety for use in foods would be anticipated.